Endocrine Abstracts

A 61-year-old female was referred after being found to be hypokalemic and hypomagnesemic on routine blood test by her GP. Her low potassium of 2.7 has been persisting in spite of treatment with Kay-Cee-L. She denies using laxatives, diuretics, or excess liquorice. She reports intermittent episodes of diarrhea and nocturnal cramps. On examination, she was noted to be hypertensive. A full hormonal profile including 5 HIAA, 24 h urine catecholamines and coeliac screen were negative. Colonoscopy was normal. Her plasma renin was elevated with a normal aldosterone: renin ratio. A CT scan of her abdomen to rule out adrenal adenoma was also normal.

She was referred to a renal physician to rule out renal tubular defect. Her 24 h urine excretion was 115 mmol/24 h with serum potassium of 3.0 showing inappropriate urine potassium wasting in the context of hypokalemia. Gitelman syndrome was considered and molecular testing was done. The diagnosis of Gitelman’s syndrome was confirmed when SLC12A3 mutations were detected. She was commenced on Amiloride and carrier testing was done on her sister.

Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis with hypocalciuria and hypomagnesemia. It is caused by loss of function of sodium–chloride symporter in the distal convoluted tubule and by the presence of the homozygous mutation in the SLC12A3 gene. Patients may complain of mild muscular cramps or weakness expressed as fatigue or irritability. Tetany and paralysis have also been reported. The surreptitious abuse of diuretics (or laxatives) remains the commonest differential diagnosis.

The treatment can be difficult, as the degree of salt wasting may be severe. Aggressive replacement of salt, and potassium in particular, is essential. Some patients respond well to the administration of indomethacin, especially in type II Bartter syndrome. Magnesium supplementation is also a useful adjunct.